Multidisciplinary Multidisciplinary Approaches to Anxiety and Approaches to Anxiety and

DepressionDepression

Sara L. Warber, MDSara L. Warber, MDGlenn Burdick, PhD Glenn Burdick, PhD

Brodie Burris, MSTCMBrodie Burris, MSTCMCaroline Richardson, MDCaroline Richardson, MD

St. John’s Wort & Depression Meta-analysis: 23 studies, 1757 ptsMeta-analysis: 23 studies, 1757 pts Mild-mod depressionMild-mod depression

Superior to placebo, rrr =2.67 (1.78-4.01)Superior to placebo, rrr =2.67 (1.78-4.01) As effective as TCA’s , rrr=1.10 (0.93-1.31)As effective as TCA’s , rrr=1.10 (0.93-1.31) Fewer side effects than TCA’sFewer side effects than TCA’s Dose: 0.4-2.7 mg Hypericin (standardized Dose: 0.4-2.7 mg Hypericin (standardized

extract) extract)

Linde K, et al. BMJ 1996;313:253-8

St. John’s Wort and Sertraline Ineffective! Multi-center, randomized controlled trialMulti-center, randomized controlled trial St. John’s Wort vs. sertralineSt. John’s Wort vs. sertraline ( (Zoloft) vs. Zoloft) vs.

placeboplacebo 8 week treatment period, 360 subjects8 week treatment period, 360 subjects No difference in Hamilton Depression ScaleNo difference in Hamilton Depression Scale Significant difference in side effectsSignificant difference in side effects

Placebo < SJW < ZoloftPlacebo < SJW < Zoloft

JAMA 2000; 287:1807-14

St. John’s Wort - Toxicology

Side effectsSide effects Theoretical risk - sunburnTheoretical risk - sunburn

Herb-drug interactionsHerb-drug interactions Studies - digoxin, protease inhibitors, TCAsStudies - digoxin, protease inhibitors, TCAs Case reports - cyclosporine, warfarin, oral Case reports - cyclosporine, warfarin, oral

contraceptives, theophylline, SSRIs contraceptives, theophylline, SSRIs Theoretical - ironTheoretical - iron

Facts & Comparisons Review of Natural Products, Dec 2000.

Kava (Piper methystictum) German Commission EGerman Commission E

mild anxietymild anxiety to induce sleepto induce sleep

Fat-soluble lactonesFat-soluble lactones kavalactone most kavalactone most

effectiveeffective

Kavalactone’s actionsKavalactone’s actions sedativesedative anticonvulsantanticonvulsant analgesicanalgesic

Powdered rootPowdered root 60-210 mg kavalactones daily (max 300mg/d)60-210 mg kavalactones daily (max 300mg/d)

Kava - Toxicology

Side effects (2.3%) Side effects (2.3%) headache, dry scaly dermopathy, GI distressheadache, dry scaly dermopathy, GI distress

Allergic rashesAllergic rashes 3 cases of dystonic reactions3 cases of dystonic reactions 25 cases of liver toxicity25 cases of liver toxicity Drug interactionsDrug interactions

Case report - sedative/hypnoticsCase report - sedative/hypnotics Theoretical - other CNS active drugsTheoretical - other CNS active drugs

SAMe (S-adenosyl-L-methionine)

For depression, osteoarthritis, fibromyalgiaFor depression, osteoarthritis, fibromyalgia Rationale: methyl donor on paths of monoamines, Rationale: methyl donor on paths of monoamines,

neurotransmitters, & phospholipidsneurotransmitters, & phospholipids Depression: 200 - 800 mg 2x/dayDepression: 200 - 800 mg 2x/day Meta-analysis: superior to placebo, equal to TCAsMeta-analysis: superior to placebo, equal to TCAs Side effects: flatulence, nausea, vomiting, Side effects: flatulence, nausea, vomiting,

diarrhea, anxiety, hypomaniadiarrhea, anxiety, hypomania If used w/ other anti-depressant If used w/ other anti-depressant serotonin serotonin

syndromesyndrome

Folate & Vitamin B12

Levels low in 1/3 of depressed personsLevels low in 1/3 of depressed persons Rationale: methyl donors, Rationale: methyl donors, SAMe SAMe 800 micrograms of each (much higher 800 micrograms of each (much higher

doses used in studies)doses used in studies) High dose Folate: alters sleep pattern, vivid High dose Folate: alters sleep pattern, vivid

dreaming, irritability, seizure, GI dreaming, irritability, seizure, GI disturbance, bitter taste in mouthdisturbance, bitter taste in mouth

Vitamin B6

Low in depressed patients (esp if taking Low in depressed patients (esp if taking estrogens)estrogens)

Rationale: essential in serotonin synthesisRationale: essential in serotonin synthesis Vitamin B Complex 100 – provides 100 mg Vitamin B Complex 100 – provides 100 mg

of major B vitamins of major B vitamins 200 mg daily 200 mg daily neurotoxicity neurotoxicity

5-HTP (Hydroxytryptophan)

Rationale: intermediate on pathway of Rationale: intermediate on pathway of tryptophan to serotonin, 70% conversiontryptophan to serotonin, 70% conversion

Also Also endorphins & catecholamines endorphins & catecholamines 100-200mg 3x/day, enteric coated100-200mg 3x/day, enteric coated As effective as SSRIs & TCAs As effective as SSRIs & TCAs Avoid use w/ other antidepressants Avoid use w/ other antidepressants

serotonin syndromeserotonin syndrome

Treating Depression with Physical Activity

Caroline R. Richardson, MDCaroline R. Richardson, MDDepartment of Family MedicineDepartment of Family MedicineVA Health Services Research and VA Health Services Research and

Development Center Development Center

Blumenthal et alexercise vs. medication

156 men and women 156 men and women Over 50 years oldOver 50 years oldMajor depressive disorder by clinical interview, BDI, HAM-DMajor depressive disorder by clinical interview, BDI, HAM-D

Randomized to – aerobic exercise (n=53),Randomized to – aerobic exercise (n=53), - Zoloft ( n = 48) or - Zoloft ( n = 48) or

- aerobic exercise + Zoloft (n=55)- aerobic exercise + Zoloft (n=55)For 16 weeksFor 16 weeks

Blumenthal et al 1999 Archives of Internal MedicineBlumenthal et al 1999 Archives of Internal Medicine

The Exercise Intervention

3 supervised exercise sessions / week3 supervised exercise sessions / week

10 minute warm up10 minute warm up 30 minutes walking or jogging at 70 to 85% 30 minutes walking or jogging at 70 to 85%

of heart rate reserve.of heart rate reserve. 5 minute cool down5 minute cool down

16 weeks16 weeks

Blumenthal’s Results

Blumenthal et al Archives of Internal Medicine 1999:159:2349-2356.

Blumenthal’s Conclusion

Exercise is as good as Zoloft in the treatment Exercise is as good as Zoloft in the treatment of Depression.of Depression.

Correct Conclusion

Among highly motivated but depressed Among highly motivated but depressed individuals, those who can successfully individuals, those who can successfully participate in a structured exercise program participate in a structured exercise program will probably significantly decrease their will probably significantly decrease their depressive symptoms. depressive symptoms.

Meta-Analysis 14 Randomized Controlled Trials14 Randomized Controlled Trials

All but two studies showed an independent, All but two studies showed an independent, statistically and clinically significant improvement in statistically and clinically significant improvement in depressive symptoms.depressive symptoms.

Effect Size -1.1 (95% CI -1.5 to -0.7)Effect Size -1.1 (95% CI -1.5 to -0.7) Comparing Exercise to No treatment ControlComparing Exercise to No treatment Control

Lawlor, DA BMJ March 2001Lawlor, DA BMJ March 2001

100’s of Observational Studies

People who are not depressed now but are People who are not depressed now but are physically active now are less likely to be physically active now are less likely to be depressed in the future.depressed in the future.

Physical Activity reduces depression Physical Activity reduces depression relapserelapse

College students who were physically College students who were physically active are less likely to become depressed active are less likely to become depressed laterlater

One more point.

We know that it is hard to start an exercise We know that it is hard to start an exercise program and harder to stick with it.program and harder to stick with it.

How many of our depressed patients How many of our depressed patients successfully initiate and maintain a successfully initiate and maintain a medication program? 20% to 60% stop medication program? 20% to 60% stop taking med in 1taking med in 1stst week. week.

How Can You Help Depressed Patients Become More Active Recommend exercise and say that there are some Recommend exercise and say that there are some

clinical trials showing exercise reduces depression clinical trials showing exercise reduces depression symptoms.symptoms.

Write out an exercise prescription along with the Write out an exercise prescription along with the anti-depressant scriptanti-depressant script

Discuss types of exercise, Ways of fitting in Discuss types of exercise, Ways of fitting in exercise, How to get startedexercise, How to get started

PEDOMETERS

Count Daily Steps and record on a calendarCount Daily Steps and record on a calendar Bring in Calendar to review after one weekBring in Calendar to review after one week Obese patients may not get accurate step countsObese patients may not get accurate step counts Caution with 10,000 steps a day target!Caution with 10,000 steps a day target! Wear the pedometer all day every dayWear the pedometer all day every day

Digi-walker SW200 ($20.00)Digi-walker SW200 ($20.00)

Watch out for Biases

Who do we think will not or should not Who do we think will not or should not exerciseexercise Poor patientsPoor patients Sick patientsSick patients Minority GroupsMinority Groups Older patientsOlder patients Depressed PatientsDepressed Patients

More Reasons for Depressed Patients to Exercise Medications for Depression cause weight Medications for Depression cause weight

gain, diabetesgain, diabetes Number 1 cause of death in depressed Number 1 cause of death in depressed

patients is still heart disease.patients is still heart disease. Diabetes is about 2 x as prevalent in Diabetes is about 2 x as prevalent in

depressed patients as it is among non-depressed patients as it is among non-depressed patients.depressed patients.